신경 질환 및 뇌졸중의 국립 연구소, -이 작품은 일반 의료 과학 국립 연구소 (U54GM104942 리드 / 잉글 러 - Chiurazzi)에 의해 지원되었다 (애쉬 - R01NS33249, R01NS63249 및 R01NS79374), 코 브레 (잉글 러 - Chiurazzi - P20GM109098) 알츠하이머 협회 (리드 - NIRG-12-242187), WVU 교수 연구 상원 그랜트 (리드), 의학 딘의 사무실의 WVU 대학 (잉글 러 - Chiurazzi)에서 WVU PSCOR 보조금 (리드) 및 내부 자금. 내용은 전적으로 저자의 책임이며 반드시 NIH 또는 알츠하이머 협회의 공식 견해를 대변하지 않습니다.

<ol>
	<li>Ramsden, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-dependent+neurofibrillary+tangle+formation,+neuron+loss,+and+memory+impairment+in+a+mouse+model+of+human+tauopathy+(P301L).">Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L).</a> The Journal of Neuroscience. 25, 10637-10647 (2005).</li><li>Attar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+shortened+barnes+maze+protocol+reveals+memory+deficits+at+4-months+of+age+in+the+triple-transgenic+mouse+model+of+Alzheimer's+disease.">A shortened barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease.</a> PLoS One. 8, e80355 (2013).</li><li>Johnson, J. M., Bailey, J. M., Johnson, J. E., Newland, M. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Performance+of+BALB/c+and+C57BL/6+mice+under+an+incremental+repeated+acquisition+of+behavioral+chains+procedure.">Performance of BALB/c and C57BL/6 mice under an incremental repeated acquisition of behavioral chains procedure.</a> Behavioural Processes. 84, 705-714 (2010).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> What's wrong with my Mouse Behavioral phenotyping of transgenic and knockout mice. , 94-95 (2000).</li><li>Westerman, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+between+abeta+and+memory+in+the+Tg2576+mouse+model+of+Alzheimer's+disease.">The relationship between abeta and memory in the Tg2576 mouse model of Alzheimer's disease.</a> The Journal of Neuroscience. 22, 1858-1867 (2002).</li><li>D'Hooge, R., De Deyn, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+the+morris+water+maze+in+the+study+of+learning+and+memory.">Applications of the morris water maze in the study of learning and memory.</a> Brain Research Reviews. 36, 60-90 (2001).</li><li>Santa Cruz, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tau+suppression+in+a+neurodegenerative+mouse+model+improves+memory+function.">Tau suppression in a neurodegenerative mouse model improves memory function.</a> Science. 309, 476-481 (2005).</li><li>Hunsberger, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+size+of+memory+deficits+in+mice+with+adult-onset+P301L+tau+expression.">Effect size of memory deficits in mice with adult-onset P301L tau expression.</a> Behavioural Brain Research. 272, 181-195 (2014).</li><li>Yue, M., Hanna, A., Wilson, J., Roder, H., Janus, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sex+difference+in+pathology+and+memory+decline+in+rTg4510+mouse+model+of+tauopathy.">Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy.</a> Neurobiology of Aging. 32, 590-603 (2011).</li><li>Sandi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+and+mechanisms+of+action+of+glucocorticoid+involvement+in+memory+storage.">The role and mechanisms of action of glucocorticoid involvement in memory storage.</a> Neural plasticity. 6, 41-52 (1998).</li><li>H&#246;lscher, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=C.+impairs+performance+in+spatial+water+maze+learning+tasks.">C. impairs performance in spatial water maze learning tasks.</a> Behavioural Brain Research. 100, 225-235 (1999).</li><li>Morris, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developments+of+a+water-maze+procedure+for+studying+spatial+learning+in+the+rat.">Developments of a water-maze procedure for studying spatial learning in the rat.</a> Journal of Neuroscience Methods. 11, 47-60 (1984).</li><li>Reed, M. N., Liu, P., Kotilinek, L. A., Ashe, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+size+of+reference+memory+deficits+in+the+morris+water+maze+in+Tg2576+mice.">Effect size of reference memory deficits in the morris water maze in Tg2576 mice.</a> Behavioural Brain Research. 212, 115-120 (2010).</li><li>Huang, Y., Zhou, W., Zhang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bright+lighting+conditions+during+testing+increase+thigmotaxis+and+impair+water+maze+performance+in+BALB/c+mice.">Bright lighting conditions during testing increase thigmotaxis and impair water maze performance in BALB/c mice.</a> Behavioral Brain Research. 226, 26-31 (2012).</li><li>Ivonen, H., Nurminen, L., Harri, M., Tanila, H., Puolivali, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypothermia+in+mice+tested+in+Morris+water+maze.">Hypothermia in mice tested in Morris water maze.</a> Behavioural Brain Research. 141, 207-213 (2003).</li><li>Rubinow, M. J., Arseneau, L. M., Beverly, J. L., Juraska, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+estrous+cycle+on+water+maze+acquisition+depends+on+the+temperature+of+the+water.">Effect of estrous cycle on water maze acquisition depends on the temperature of the water.</a> Behavioral Neuroscience. 118 (4), 863-868 (2004).</li></ol>

저자가 공개하는 게 없다.

MWM 태스크 널리 공간 학습 및 기억을 평가하는 데 사용된다. 그러나,이 작업의 안정성은 많은 요인들에 의해 영향을 배경 균주 및 테스트 환경 모두의 최적화를 필요로 할 수있다. 도 4는 동일한 트레이닝 프로토콜에 나타낸 두 개의 다른 테스트 실 (동등한 크기 및 레이아웃)에 사용되는 시각적 적용된 상당히 상이한 프로브의 성능을 수득 하였다. 테스트 룸의 많은 기능이 공간 큐 <su...

형질 전환 마우스 모델은 알츠하이머 병 (AD)의 병태 생리학뿐만 아니라, 치료 적 개입의 가능성을 평가하는 수단이되어왔다. 이러한 모리스 물 미로 (MWM)인지 적 작업은 일반적으로 기억력 결핍의 분자 상관 관계를 파악하고 전임상 약물의 효능을 평가하기 위해 이러한 모델과 함께 사용된다. 이는인지 작업의 동적 범위는 치료 효과 미묘한 검출 충분히 넓은 것이 그러나 중요하다. 광고의 마우스 모델,인지 적자는 일반적으로 나이에 따라 달라집니다, 그리고 마우스는 성능이 점진적 감소를 표시 (예를 들면, 1). 민감한 태스크인지를 사용하여 동물 노화와 관련된 비용을 줄일 이전 동물의 생명에 미묘한 차이를 검출 할 수있다. 예를 들면, 해마 의존적 반스 훈련 실험의 수를 줄이는 것이 15-5 미로 D 결과, 작업의 어려움을 증가보다 이른 나이에 3xTg 모델에서 적자의 금 속 탐은 이전에 2를보고했다. 적자 이전 검출뿐만 아니라 이것은 또한인지 결핍의 기초 분자의 변화를 식별 할 수있는 가능성이 높아, 상당한 시간과 비용 절감을 제공한다. 인지 작업의 감도에 영향을 미치는 하나의 요인은 마우스 모델의 유전 배경 균주이다. 예를 들어, BALB / c 마우스는 C57BL / 6 (3)과 같은 다른 균주에 비해 과제 학습 및 기억에 우수한 성능을 나타낸다. F1 FVB / N X 129S6 배경은 AD의 가장 널리 사용되는 모델 Tg2576 및 RTG (TauP301L) 4510 모델이 사용된다. 이 균주는 B6 / SJL 마우스 (4)를 포함하여 다른 균주에 MWM 상대적으로 우수한 학습 능력을 나타낸다. 이 때문에 우수한 학습 능력, 광범위한 훈련 후 단일 프로브의 사용은 오버 - 트레이닝으로 인한 그룹 차이를 마스크 할 수있다. 또한, sensitivit프로브 시험의 Y는 연령에 따라 달라질 수 있습니다. 우리는 이전에 이전 프로브 시험은 제한 숨겨진 플랫폼 훈련 후,보다 젊은 형질 전환 유전자 음성 한배의 새끼 컨트롤에 비해 젊은 Tg2576의 차이에 더 민감 더 광범위한 훈련 (5) 다음에 삽입 프로브 시험 있음을 보여 주었다. 이전 프로브 시험 5보다 대조적으로, 광범위한 교육을 다음과 같은 검사 시험은 이전 한배 새끼에 비해 Tg2576 마우스 이전 (20 ~ 25 월)에 더 민감하다. 길이 시험이 수행되고, 특정 프로브 시험의 감도 연령 의존적 인 경우 특히 훈련 ​​내내 프로브 시험을 산재하여 민감한 재판이 식별 될 가능성이 증가된다. 1 F1 FVB / N (X)의 우수한 성능을 보여준다 더 광범위한 훈련 프로토콜에서 훈련 B6 / SJL 배경의 마우스에 비해이 변형에 최적화 된 프로토콜에 따라 129S6 마우스. MWM은일반적으로 시간과 실험실 (6) 모두에서 재현 할 수있는 신뢰할 수있는 수단을 제공하기 위해 생각했다. 예를 들어, 원래 우리의 미네소타 실험실 1,7에서 사용되는 기본 프로토콜이 성공적으로 웨스트 버지니아 대학 8에 약간의 수정으로 구현되었습니다. 마찬가지로, 손상 동등한 수준 무균 또는 통상 조건 하에서 구 수납 경우 한배 새끼를 제어하기 위해 4510 생쥐 상대 RTG (TauP301L)에서 관찰되었다. 그러나, 테스트 환경 MWM 태스크의 민감도에 영향을 미칠 수있다. 같은 실내 조명, 환기구, 온도 구배 및 소음 등의 모든 요소가 궁극적으로 성능에 영향을 미칠 수있는 환경 단서 4에 기여한다. 우리 미네소타 실험실 동물 사육장은 신축 이동 하였을 때, 최대 야생형 성능의 38 % 감소는 실질적으로 작업 및 트랜스 - 관련 결핍을 탐지 할 수있는 능력의 동적 범위를 감소가 관찰되었다. PE의 변화rformance 동등한 크기 및 구성으로 검사실을 설계하고, 동일한인가 시각적 큐를 사용에도 불구하고 발생 하였다. 본래의 프로토콜 A &quot;재 최적화가&quot;새로운 테스트 환경에서 MWM 태스크의 동적 범위를 증가시키기 위해 요구되었다. 여기에 F1 FVB / N와 함께 사용하기위한 맞춤형 원래 프로토콜은 129S6 배경 5 설명 X. 일부 연구는 응력을 제시하기 때문에 성능 (11)이 스트레스 유도 결손 완화 불량한 MWM 성능 (10) 및 사전 처리와 연결되어, 사전 처리 프로토콜은 풀의 도입 및 제거 전에 MWM 테스트 행에 쥐를 순응하도록 설계되었다 . 사전 처리 후, 마우스 제기 플랫폼 플래그가 표시되는 볼 플랫폼 교육을 받다. 눈에 보이는 플랫폼 훈련은 감각 이상과 관련된 성능 문제로 쥐를 식별하는 데 사용됩니다. 제자에 설명 된 배제 기준을 사용하여ocol 섹션, 성능 무능한 마우스 숨겨진 플랫폼 교육 및 프로브 시험 이후의 시험에서 제거됩니다. 감각 성능 데이터에서 고려되기 때문에 숨겨진 플랫폼 교육 및 프로브 시험에서 장애인지 적자로 해석됩니다. 가시 플랫폼 훈련 종료 후, 마우스는 플랫폼을 물에 잠긴 외부 큐에 대해 동일한 위치에 유지된다 숨겨진 플랫폼 트레이닝을 시작. 플랫폼 (프로브 시험)을 제거하는 시험이 추가 교육의 영향을 평가하기 위해 숨겨진 플랫폼 교육 전반에 걸쳐 산재되어있다. 프로브 실험은 하루의 시작 부분에서 발생하기 때문에 추가적인 숨겨진 플랫폼 트레이닝 전에, 프로브 실험은 20 시간 지연에 따라 플랫폼의 위치를 기억하는 동물의 능력을 측정하고, 기준 메모리 (12)의 측정 값을 고려 하였다. 마지막으로, 방법은이 프로토콜은 원래 다시 최적화 될 때 테스트 환경 변화중단 제어 성능이 설명되어 있습니다.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Viewer Tracking software</td>
			<td>Biobserve</td>
			<td></td>
			<td>This particular software is not a requirement - there are other tracking systems available</td>
		</tr>
		<tr>
			<td>Pre-handling pool</td>
			<td></td>
			<td></td>
			<td>Dimensions approximately 1 foot wide x 2 feet long x 1.5 feet deep</td>
		</tr>
		<tr>
			<td>Plastic beaker</td>
			<td></td>
			<td></td>
			<td>1 liter</td>
		</tr>
		<tr>
			<td>Scoop</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Small net</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>White circular tub</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Non-toxic white tempera paint</td>
			<td></td>
			<td></td>
			<td>Any color can paint can be used; must completely cover the hidden platform</td>
		</tr>
		<tr>
			<td>Platform</td>
			<td></td>
			<td></td>
			<td>Color should contrast that of maze</td>
		</tr>
		<tr>
			<td>Curtain rod</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Curtains</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse performance tracking software</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Circular tub</td>
			<td></td>
			<td></td>
			<td>Uusally white in color; approximately 4 feet in diamater</td>
		</tr>
		<tr>
			<td>Platform</td>
			<td></td>
			<td></td>
			<td>Painted same color as the water</td>
		</tr>
	</tbody>
</table>

morris water maze test: optimization for mouse strain and testing environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

우리는 그림 3은 베타 - 아밀로이드 (Tg2576 마우스) 및 돌연변이 P301L 타우 공간 참조 메모리 (RTG (TauP301L) 4510 마우스) (예를 들면, 1,5,7,8).의 효과를 연구하기 위해 모리스 물 미로를 사용했다 대표적인 결과는 모터 및 시각적 능력을 평가하기 위해 테스트 환경 A.을 이용하는, 학습 및 기억 8 성인 발병 P301L 타우 발현의 효과를 조사 연구에서보고 된 마우스는 각 트?...

Watch this Scientific Journal Video about Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment at JoVE.com

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

모리스 물 미로 테스트 : 마우스 스트레인 및 테스트 환경을위한 최적화

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

morris-water-maze-test-optimization-for-mouse-strain-testing

Research

JoVE Journal

Behavior

21.3K 조회수.  West Virginia University.  This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences. 

비디오: Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

Shallow Water (Paddling) Variants of Water Maze Tests in Mice

When Richard Morris devised his water maze in 19817, most behavioral work was done in rats. However, the greater understanding of mouse genetics led to the mouse becoming increasingly important. But researchers found that some strains of mutant mice were prone to problems like passively floating or diving when they were tested in the Morris water maze11. This was unsurprising considering their natural habitat; rats swim naturally (classically, the "sewer rat"), whereas mice evolved in the dry areas of central Asia.
To overcome these problems, it was considered whether shallow water would be a sufficient stimulus to provide escape motivation for mice. This would also avoid the problems of drying the small creatures with a towel and then putting them in a heated recovery chamber to avoid hypothermia, which is a much more serious problem than with rats; the large ratio of surface area to volume of a mouse makes it particularly vulnerable to rapid heat loss.
Another consideration was whether a more natural escape strategy could be used, to facilitate learning. Since animals that fall into water and swim away from the safety of the shore are unlikely to pass on their genes, animals have evolved a natural tendency to swim to the edge of a body of water. The Morris water maze, however, requires them to swim to a hidden platform towards the center of the maze - exactly opposite to their evolved behavior. Therefore the paddling maze should incorporate escape to the edge of the apparatus. This feature, coupled with the use of relatively non-aversive shallow water, embodies the "Refinement" aspect of the "3 Rs" of Russell and Burch8.
Various types of maze design were tried; the common feature was that the water was always shallow (2 cm deep) and escape was via a tube piercing the transparent wall of the apparatus. Other tubes ("false exits") were also placed around the walls but these were blocked off. From the inside of the maze all false exits and the single true exit looked the same. Currently a dodecagonal (12-sided) maze is in use in Oxford, with 12 true/false exits set in the corners. In a recent development a transparent paddling Y-maze has been tested successfully.

Shallow Water Paddling Variants of Water Maze Tests in Mice

Mice can swim, but many strains appear to find this activity stressful. To overcome this problem mazes have been devised where escape from shallow water is used to motivate behaviour. These have been demonstrated to support learning at least as good as the traditional and widely used Morris water maze.

마우스의 물 미로 시험의 얕은 물 (패들링) 변종

When Richard Morris devised his water maze in 19817, most behavioral work was done in rats. However, the greater understanding of mouse genetics led to ...

연구

행동분석학

Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs.

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food ...

Barnes Maze Testing Strategies with Small and Large Rodent Models

Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land (Barnes) mazes. Improved performance over sessions or trials is thought to reflect learning and memory of the escape cage/platform location. Considered less stressful than water mazes, the Barnes maze is a relatively simple design of a circular platform top with several holes equally spaced around the perimeter edge. All but one of the holes are false-bottomed or blind-ending, while one leads to an escape cage. Mildly aversive stimuli (e.g.&#160;bright overhead lights) provide motivation to locate the escape cage. Latency to locate the escape cage can be measured during the session; however, additional endpoints typically require video recording. From those video recordings, use of automated tracking software can generate a variety of endpoints that are similar to those produced in water mazes (e.g.&#160;distance traveled, velocity/speed, time spent in the correct quadrant, time spent moving/resting, and confirmation of latency). Type of search strategy (i.e.&#160;random, serial, or direct) can be categorized as well. Barnes maze construction and testing methodologies can differ for small rodents, such as mice, and large rodents, such as rats. For example, while extra-maze cues are effective for rats, smaller wild rodents may require intra-maze cues with a visual barrier around the maze. Appropriate stimuli must be identified which motivate the rodent to locate the escape cage. Both Barnes and water mazes can be time consuming as 4-7 test trials are typically required to detect improved learning and memory performance (e.g.&#160;shorter latencies or path lengths to locate the escape platform or cage) and/or differences between experimental groups. Even so, the Barnes maze is a widely employed behavioral assessment measuring spatial navigational abilities and their potential disruption by genetic, neurobehavioral manipulations, or drug/ toxicant exposure.

The dry-land Barnes maze is widely used to measure spatial navigation ability in response to mildly aversive stimuli. Over consecutive days, performance (e.g.&#160;latency to locate escape cage) of control subjects improves, indicative of normal learning and memory. Differences between rats and mice necessitate apparatus and methodology changes that are detailed here.

크고 작은 설치류 모델 바네스 미로 테스트 전략

Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land ...

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms.
Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; &#167;4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; &#167;4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces.
Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems.

The goal of this protocol is to investigate spatial cognition in rodents. The double-H water maze is a novel test, which is particularly useful to elucidate the different components of learning, consolidation and memory, as well as the interplay of memory systems.

더블 H 미로 : 설치류의 강력한 행동 학습에 대한 테스트 및 메모리

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their ...

A Protocol for Housing Mice in an Enriched Environment

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of &#8216;toys&#8217; to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer.

Environmental enrichment for mice requires a complex and challenging setup, as well as comprehensive husbandry and handling techniques to assure robust metabolic and anti-cancer effects in the mice. This protocol provides detailed procedures to reproduce the above mentioned effects in mice.

풍부한 환경에서의 주택 마우스를위한 프로토콜

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent ...

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory (designed specifically for mice and requiring no swimming) has been shown previously to successfully distinguish between controlled cortical impact-induced TBI mice and sham controls. Here, a detailed protocol for this task is presented. The RWT maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze are lined with nine escape holes placed above the floor of the apparatus, and mice are trained to use visual cues to locate the escape hole that leads out of the maze. The maze is filled with an inch of cold water, sufficient to motivate escape but not deep enough to require that the mouse swim. The acquisition period takes only four training days, with a test of memory retention on day five and a long-term memory test on day 12. The results reported here suggest that the RWT maze is a feasible alternative to rat-validated, swimming-based cognitive tests in the assessment of spatial memory deficits in mouse models of TBI.

Here we present a protocol for a mouse-specific test of cognition that does not require swimming. This test can be used to successfully distinguish controlled cortical impact-induced traumatic brain injury mice from sham controls.

방사형 워터 트레드 미로를 이용한 외상성 뇌 손상의 마우스 모델에서 공간 기억 장애의 평가

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

Testing Animal Anxiety in Rats: Effects of Open Arm Ledges and Closed Arm Wall Transparency in Elevated Plus Maze Test

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral science, conflicting outcomes are often provided from different laboratories. To identify reasons for the different outcomes, we previously focused on arm features, which differ between laboratories, most notably the presence/absence of ledges at the sides of open arms and the transparency/opaqueness of closed arm walls. In a previous report, we used a custom designed container to compare rat behavior on different combinations of open and closed arm designs under otherwise identical experimental conditions, and showed that differences in arm features interfere with experimental outcomes. In brief, open arm ledges significantly increased anxiety-like behavior in rats, while transparent arms may also have decreased this behavior. Furthermore, we verified a higher detection sensitivity of the effect of an anxiolytic drug in a combination of no-ledged open arm + opaque walled closed arm compared with a combination of ledged open arm + transparent walled closed arm. In this report, we introduce our protocol for the elevated plus maze test, together with discussion of the key results from the previous report and our experimental experience. We believe this report will provide useful information for researchers who have employed or who plan to use the elevated plus maze in their studies.

Rats' anxiety-like behavior tested by the elevated plus maze varies highly depending on the testing environment. Here we show how apparatus settings, especially arm structure, affect behavior on the maze, and we explain a reliable protocol to detect effects of anxiolytic drugs. This report will contribute to anxiety research.

쥐에서 동물 불안을 테스트: 오픈 팔 레와 닫힌된 팔 벽 투명성 높은 플러스 미로 테스트

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral ...

Testing for Metacognitive Responding Using an Odor-based Delayed Match-to-Sample Test in Rats

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, numerous behavioral tasks have been created, many of which utilize an option to decline memory tests. To assess metamemory in rats, we utilized this decline-test option paradigm by adapting previous visual delayed-match-to-sample tests (DMTS)1,2 developed for primate species to an odor-based test suitable for rodents. First,&#160;rats are given a sample to remember by digging in a cup of scented sand. After a delay, the rat is presented with four distinctly scented cups, one of which contains the identical scent experienced during the sample; if this matching cup is selected, then the rat obtains a preferred, larger reward. Selection of any of the other three non-matching sand-filled scented cups results in no reward. Retention intervals are individually titrated such that subjects perform between 40 and 70% correct, therefore ensuring rats sometimes remember and sometimes forget the sample. Here, the operational definition of metamemory is the ability to distinguish between the presence and absence of memory through behavioral responding. Towards this end, on two-thirds of trials, a decline option is presented in addition to the four choice cups (choice trials). If the decline-test option- an unscented colored sand cup, is selected, the subject receives a smaller less-preferred reward and avoids the memory test. On the remaining third of trials, the decline-test option is not available (forced trials), causing subjects to guess the correct cup when the sample is forgotten. On choice tests, subjects that know when they remember should select the decline option when memory is weak rather than take the test and choose incorrectly. Therefore, significantly higher performance on chosen tests as compared to forced memory tests is indicative of the adaptive use of the decline-test response and metacognitive responding.

This protocol describes a method for investigating the possibility of metamemory, or memory awareness, in rodents. The odor-based delayed-matching-to-sample paradigm is a novel, ecologically-relevant behavioral test useful for determining the extent to which rodents can adaptively respond based on cognitively monitoring the strength of their memory states.

쥐에 일치 샘플 테스트 지연 Metacognitive 냄새 기반을 사용 하 여 응답에 대 한 테스트

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, ...

Measuring Active and Passive Tameness Separately in Mice

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two behavioral components: a reluctance to avoid humans (passive tameness) and a motivation to approach humans (active tameness). To quantify these components in mice, we previously developed behavioral tests for active tameness, passive tameness, and the willingness to stay on a human hand, each designed to be completed within 3 min. The data obtained were used for selective breeding, with a large number of mice analyzed per generation. The active tameness test measures the movement of the mouse toward a human hand and the contact it engages in. The passive tameness test measures the duration of time that a mouse tolerates human touch. In the stay-on-hand test, a mouse is placed on a human hand and touched slowly using the thumb of that hand; the duration of time that the animal remains on the hand is measured. Here, we describe the test set-up and apparatus, explain the procedures, and discuss the appropriate data analysis. Finally, we explain how to interpret the results.

Tameness in animals includes a reduction of avoidance responses to humans (passive tameness) and an increase in active approaches to humans (active tameness). Here, we describe detailed protocols for three behavioral tests (active tameness, passive tameness, and stay-on-hand tests) to separately measure the active and passive tameness of mice.

마우스에서 별도로 측정 능동 및 수동 Tameness

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two ...

Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements

The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The purpose of the method is to document the effect of various potential anxiolytic treatments on laboratory rodent models. The EPM test is based on the rodents&#39; proclivity toward protected, enclosed dark spaces and unconditioned fear of open spaces and heights, and their innate intense motivation to explore novel environments. The EPM test is a widely used behavioral test for investigating the anxiolytic or anxiogenic responses of rodents given drugs that are known to affect behavior. Observation demonstrating a decreased proportion of time spent on closed arms, an increased proportion of time spent on open arms, a reduced number of entries to closed arms, and an elevated number of entries to open arms measured by the EPM test may reflect reduced anxiety levels. Using this method, the effect of exogenous ketone supplements on anxiety-related behavior is tested in Sprague Dawley (SPD) rats. Exogenous ketone supplements are chronically fed to the rats for 83 days or subchronically and acutely orally gavaged, daily for 7 days, before conducting the EPM test. Behavioral data collection is performed using the SMART video tracking system by a blinded observer at the end of the treatments. The main findings indicate that the EPM test is an effective method to detect the ketone supplement-induced anxiolytic effect and can be considered a sensitive measure to assess changes in anxiety behavior associated with drug- or metabolic-based therapies.

Here, we present a protocol to investigate changes in the anxiety level of rodent animal models. The elevated plus maze (EPM) test, used together with a video tracking software, provides a reliable method to document the effect of various potential anxiolytic treatments in preclinical laboratory scenarios.

The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The ...